Identification of new aryl hydrocarbon receptor (AhR) antagonists using a zebrafish model

Bioorg Med Chem. 2019 Oct 1;27(19):115014. doi: 10.1016/j.bmc.2019.07.030. Epub 2019 Jul 18.

Abstract

A new series of 1,3-diketone, heterocyclic and α,β-unsaturated derivatives were synthesized and evaluated for their AhR antagonist activity using zebrafish and mammalian cells. Compounds 1b, 2c, 3b and 5b showed significant AhR antagonist activity in a transgenic zebrafish model. Among them, compound 3b, and 5b were found to have excellent AhR antagonist activity with IC50 of 3.36 nM and 8.3 nM in a luciferase reporter gene assay. In stem cell proliferation assay, compound 5b elicited marked HSC expansion.

Keywords: Antagonist; Aryl hydrocarbon receptor (AhR); Stem cell; Zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / antagonists & inhibitors*
  • COS Cells
  • Cell Proliferation / drug effects
  • Chalcones / chemical synthesis
  • Chalcones / pharmacology*
  • Chlorocebus aethiops
  • Humans
  • Receptors, Aryl Hydrocarbon / antagonists & inhibitors*
  • Stem Cells / drug effects
  • Zebrafish
  • Zebrafish Proteins / antagonists & inhibitors*

Substances

  • AHR protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Chalcones
  • Receptors, Aryl Hydrocarbon
  • Zebrafish Proteins